Profiling DNA methylation differences between inbred mouse strains on the Illumina Human Infinium MethylationEPIC...

Area of Science:

• Epigenetics and Genomics
• Comparative Genomics
• Model Organism Research

Background:

• The Illumina Infinium MethylationEPIC array is a key tool for human DNA methylation profiling.
• No equivalent array exists for model organisms like mice, limiting cross-species epigenetic studies.
• Understanding DNA methylation in mice is crucial for modeling human diseases and biological processes.

Purpose of the Study:

• To adapt and validate the human MethylationEPIC array for profiling mouse DNA methylation.
• To assess the array's performance against established sequencing-based methods (MBD-seq, RRBS).
• To investigate differential DNA methylation in mice based on strain and age.

Main Methods:

• Targeted conserved CpG probes on the MethylationEPIC array for mouse genomes.
• Compared array data with MBD-seq and RRBS for DNA methylation analysis.
• Utilized linear regression for differential methylation analysis between mouse strains (C57BL/6J vs. DBA/2J) and age groups.
• Evaluated probe performance for quantitative sensitivity and differential methylation detection.

Main Results:

• 1.6% of EPIC probes (13,665) targeted conserved CpGs in mice, showing human-like beta-value distributions.
• High concordance (r=0.70) observed between EPIC array and MBD-seq, with superior quantitative sensitivity for the array at extreme methylation levels.
• No significant age-dependent differential methylation detected by EPIC array probes, while MBD-seq performed better. However, a top age-associated probe (cg13269407) is a human epigenetic clock CpG.
• 219 EPIC probes detected significant strain-specific differential methylation (FDR < 10%), with ~80% showing higher methylation in DBA/2J mice compared to C57BL/6J, consistent with MBD-seq data.

Conclusions:

• A small subset of MethylationEPIC array probes can reliably measure DNA methylation in mice.
• The array is effective for detecting differential methylation between mouse strains.
• While limited for age-related changes, the array offers a valuable, quantitative tool for mouse epigenome research, especially when combined with sequencing data.